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1. 发明申请

US20110065938A1 METHOD FOR THE PREPARATION OF ESCITALOPRAM 审中-公开
标题翻译：用于制备ESCITALOPRAM的方法
公开(公告)号：US20110065938A1
公开(公告)日：2011-03-17
申请号：US12781048
申请日：2010-05-17
申请人： Michael B. Sommer , Ole Nielsen , Hans Petersen , Haleh Ahmadian , Henrik Pedersen , Peter Brosen , Fiona Geiser , James Lee , Geoffrey Cox , Olivier Dapremont , Christina Suteu , Sebastian P. Assenza , Shankar Hariharan , Usha Nair
发明人： Michael B. Sommer , Ole Nielsen , Hans Petersen , Haleh Ahmadian , Henrik Pedersen , Peter Brosen , Fiona Geiser , James Lee , Geoffrey Cox , Olivier Dapremont , Christina Suteu , Sebastian P. Assenza , Shankar Hariharan , Usha Nair
IPC分类号： C07D307/87 , C07C215/32
CPC分类号： C07C215/32 , C07D307/87
摘要： A novel method is provided for the manufacture of escitalopram. The method comprises chromatographic separation of the enantiomers of citalopram or an intermediate in the production of citalopram using a chiral stationary phase such as Chiralpak™ AD or Chiralcel™ OD. Novel chiral intermediates for the synthesis of Escitalopram made by said method are also provided.
摘要翻译：提供了一种制备依他普仑的新方法。该方法包括使用手性固定相如Chiralpak TM AD或Chiralcel TM OD，对西酞普兰对映异构体或西酞普兰生产中的中间体进行色谱分离。还提供了通过所述方法制备的用于合成依他普仑的新型手性中间体。

2. 发明申请

US20050065207A1 Method for the preparation of escitalopram 审中-公开
标题翻译：艾司西酞普兰的制备方法
公开(公告)号：US20050065207A1
公开(公告)日：2005-03-24
申请号：US10483824
申请日：2002-07-12
申请人： Michael Sommer , Ole Nielsen , Hans Petersen , Haleh Ahmadian , Henrik Pedersen , Peter Brosen , Fiona Geiser , James Lee , Geoffrey Cox , Olivier Dapremont , Christina Suteu , Sebastian Assenza , Shankar Hariharan , Usha Nair
发明人： Michael Sommer , Ole Nielsen , Hans Petersen , Haleh Ahmadian , Henrik Pedersen , Peter Brosen , Fiona Geiser , James Lee , Geoffrey Cox , Olivier Dapremont , Christina Suteu , Sebastian Assenza , Shankar Hariharan , Usha Nair
IPC分类号： A61K31/343 , A61P25/24 , C07B20060101 , C07C215/32 , C07C215/34 , C07D20060101 , C07D307/87
CPC分类号： C07C215/32 , C07D307/87
摘要： A novel method is provided for the manufacture of escitalopram. The method comprises chromatographic separation of the enantiomers of citalopram or an intermediate in the production of citalopram using a chiral stationary phase such as Chiralpak™ or Chiralcel™ OD. Novel chiral intermediates for the synthesis of Escitalopram made by said method are also provided.
摘要翻译：提供了一种制备依他普仑的新方法。该方法包括使用手性固定相（例如Chiralpak TM或Chiralcel TM OD）对西酞普兰对映异构体或西酞普兰生产中的中间体进行色谱分离。还提供了通过所述方法制备的用于合成依他普仑的新型手性中间体。

3. 发明申请

US20090242486A1 SIMULATED MOVING BED CHROMATOGRAPHY FOR STRONGLY RETAINED COMPOUNDS 有权
标题翻译：用于强力保留化合物的模拟移动色谱法
公开(公告)号：US20090242486A1
公开(公告)日：2009-10-01
申请号：US12059651
申请日：2008-03-31
申请人： Olivier Dapremont
发明人： Olivier Dapremont
IPC分类号： B01D15/18
CPC分类号： B01D15/1828
摘要： Simulated moving bed (SMB) chromatography involving a series of columns serially connected in a circuit is performed in a modified protocol by dividing the columns into two groups isolated from flow communication with each other and using one of the two groups solely for extraction of the more strongly retained component from the solid phase while the other group is operated in the conventional SMB manner. The sites of introduction and withdrawal and the site of division between the two groups of columns are all rotated around the circuit as in conventional SMB chromatography, but the process is capable of separating component mixtures with non-linear isotherms and of extracting solutes that are very strongly retained on the solid phase.
摘要翻译：模拟移动床（SMB）色谱法涉及一系列串联在电路中的色谱柱，通过将色谱柱分为两组，分别与流体连通分离，并使用两组之一，仅用于提取更多从固相中强烈保留成分，而另一组以常规SMB方式操作。引入和取出的位置和两组柱之间的分割位置都像在常规SMB色谱中一样在电路周围旋转，但是该方法能够将非均匀性的非线性等温线分离组分混合物，并提取很多的溶质强烈地保留在固相上。

4. 发明授权

US08357302B2 Reaction systems with incorporated chromatography units for enhanced product recovery 有权
标题翻译：具有内置色谱单元的反应体系，用于增强产品回收率
公开(公告)号：US08357302B2
公开(公告)日：2013-01-22
申请号：US13190781
申请日：2011-07-26
申请人： Olivier Dapremont , Aslam Malik
发明人： Olivier Dapremont , Aslam Malik
IPC分类号： B01D15/08
CPC分类号： B01D15/1821 , B01D9/0045
摘要： Product yields in chemical reactions that produce a solid product from a liquid reaction mixture are improved by chromatographically separating certain key impurities from the product mixture prior to crystallization, or from the filtrate after crystallization in which case further product is crystallized from the filtrate. The removal of key impurities either before the first crystallization or between the first and second crystallizations facilitates the crystallization of product to produce a higher yield of product.
摘要翻译：通过在结晶之前色谱分离产物混合物中的某些关键杂质，或从结晶后的滤液中提取从液体反应混合物产生固体产物的化学反应中的产物产率得到改善，在这种情况下，再滤液从滤液中结晶。在第一次结晶之前或在第一次和第二次结晶之前除去关键杂质有利于产物的结晶，从而产生更高的产率。

5. 发明申请

US20060183777A1 Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts 有权
标题翻译：羟基亚氨基甲基季吡啶盐的卤代甲基醚的方法
公开(公告)号：US20060183777A1
公开(公告)日：2006-08-17
申请号：US11133740
申请日：2005-05-19
申请人： Der-Shing Huang , George Gettys , Olivier Dapremont , Aslam Malik
发明人： Der-Shing Huang , George Gettys , Olivier Dapremont , Aslam Malik
IPC分类号： A61K31/44
CPC分类号： C07D213/53 , C07D213/81
摘要： A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane in high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di (1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.
摘要翻译：通过向双卤代甲醚中加入吡啶醛肟制备1-（羟基亚氨基甲基-1-吡啶基）-3-（卤代甲基）-2-氧杂丙烷的卤化物盐，使双 - 卤代甲醚在整个过程中保持过量加成。该方法以高产率和纯度产生1-（羟基亚氨基甲基-1-吡啶基）-3-（卤代甲基）-2-氧杂丙烷的卤化物盐，这有助于其用作制备不对称取代的1,3 -di（1-吡啶基）-2-氧杂丙烷，一类通常用于各种毒性剂的解毒剂的化合物。该类的突出成员是1-（2-羟基亚氨基甲基-1-吡啶基）-3-（4-氨基甲酰基-1-吡啶基）-2-氧杂丙烷的二甲基磺酸盐。公开了使用巯基烷基官能化聚合物作为优选的金属离子清除剂，用于制造这些化合物的最终纯化步骤。

6. 发明授权

US06967259B2 Process for the preparation of Citalopram intermediate 失效
标题翻译：制备西酞普兰中间体的方法
公开(公告)号：US06967259B2
公开(公告)日：2005-11-22
申请号：US10242322
申请日：2002-09-11
申请人： Aslam A. Malik , Hasan Palandoken , Joy A. Stringer , DerShing Huang , Antonio Romero , Olivier Dapremont
发明人： Aslam A. Malik , Hasan Palandoken , Joy A. Stringer , DerShing Huang , Antonio Romero , Olivier Dapremont
IPC分类号： A61K31/343 , A61P25/24 , C07C213/00 , C07C213/10 , C07C215/34 , C07D307/87
CPC分类号： C07D307/87
摘要： The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.
摘要翻译：本发明尤其提供了一种制备已知抗抑郁药的西酞普兰的新方法。

7. 发明授权

US08809526B2 Synthesis of cyclopentaquinazolines 有权
标题翻译：环戊基喹唑啉的合成
公开(公告)号：US08809526B2
公开(公告)日：2014-08-19
申请号：US13810763
申请日：2011-07-15
申请人： James Alan Kerschen , Alexander James Bridges , Sean Mark Dalziel , Olivier Dapremont , Hyunjung Kim , Andrew S. Thompson , James Robert Zeller
发明人： James Alan Kerschen , Alexander James Bridges , Sean Mark Dalziel , Olivier Dapremont , Hyunjung Kim , Andrew S. Thompson , James Robert Zeller
IPC分类号： C07D455/00
CPC分类号： C07D455/00 , C07C227/20 , C07D239/70
摘要： A method of producing 6-amino-cyclopenta[g]quinazolines, in enantiomerically enriched form, is provided. In particular, the method may be applicable to the synthesis of N—{N-{4-[N-((6S)-2 -hydroxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclo-penta[g]quinazolin-6-yl)-N-(prop-2 -ynyl)amino]benzoyl}-L-γ-glutamyl}-D-glutamic acid (ONX-0801).
摘要翻译：提供以对映体富集形式生产6-氨基 - 环戊二烯并[g]喹唑啉的方法。特别地，该方法可适用于合成N- {N- {4- [N - （（S）-2-羟基甲基-4-氧代-3,4,7,8-四氢-6H-环 - 五（m）喹唑啉-6-基）-N-（丙-2-炔基）氨基]苯甲酰基} -L-γ-谷氨酰基} -D-谷氨酸（ONX-0801）。

8. 发明申请

US20120024785A1 REACTION SYSTEMS WITH INCORPORATED CHROMATOGRAPHY UNITS FOR ENHANCED PRODUCT RECOVERY 有权
标题翻译：具有增强色谱恢复功能的反应体系
公开(公告)号：US20120024785A1
公开(公告)日：2012-02-02
申请号：US13190781
申请日：2011-07-26
申请人： Olivier Dapremont , Aslam Malik
发明人： Olivier Dapremont , Aslam Malik
IPC分类号： B01D15/08 , B01D36/00 , B01D9/00 , B01D11/04
CPC分类号： B01D15/1821 , B01D9/0045
摘要： Product yields in chemical reactions that produce a solid product from a liquid reaction mixture are improved by chromatographically separating certain key impurities from the product mixture prior to crystallization, or from the filtrate after crystallization in which case further product is crystallized from the filtrate. The removal of key impurities either before the first crystallization or between the first and second crystallizations facilitates the crystallization of product to produce a higher yield of product.
摘要翻译：通过在结晶之前色谱分离产物混合物中的某些关键杂质，或从结晶后的滤液中提取从液体反应混合物产生固体产物的化学反应中的产物产率得到改善，在这种情况下，再滤液从滤液中结晶。在第一次结晶之前或在第一次和第二次结晶之前除去关键杂质有利于产物的结晶，从而产生更高的产率。

9. 再颁专利

USRE41898E1 Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts 有权
标题翻译：羟基亚氨基甲基季吡啶盐的卤代甲基醚的方法
公开(公告)号：USRE41898E1
公开(公告)日：2010-10-26
申请号：US12274133
申请日：2008-11-19
申请人： Der-Shing Huang , George R. Gettys , Olivier Dapremont
发明人： Der-Shing Huang , George R. Gettys , Olivier Dapremont
IPC分类号： C07D401/02
CPC分类号： C07D213/53 , C07D213/81
摘要： A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropanein high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di(1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.
摘要翻译：通过向双卤代甲醚中加入吡啶醛肟制备1-（羟基亚氨基甲基-1-吡啶基）-3-（卤代甲基）-2-氧杂丙烷的卤化物盐，使双 - 卤代甲醚在整个过程中保持过量加成。该方法产生1-（羟基亚氨基甲基-1-吡啶基）-3-（卤代甲基）-2-氧杂丙烷的卤化物盐，其产率和纯度高，这有助于其用作制备不对称取代的1,3- 二（1-吡啶基）-2-氧杂丙烷，一类通常用于各种毒性剂的解毒剂的化合物。该类的突出成员是1-（2-羟基亚氨基甲基-1-吡啶基）-3-（4-氨基甲酰基-1-吡啶基）-2-氧杂丙烷的二甲基磺酸盐。公开了使用巯基烷基官能化聚合物作为优选的金属离子清除剂，用于制造这些化合物的最终纯化步骤。

10. 发明授权

US07414135B2 Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts 有权
标题翻译：羟基亚氨基甲基季吡啶盐的卤代甲基醚的方法
公开(公告)号：US07414135B2
公开(公告)日：2008-08-19
申请号：US11133740
申请日：2005-05-19
申请人： Der-Shing Huang , George R. Gettys , Olivier Dapremont , Aslam A. Malik
发明人： Der-Shing Huang , George R. Gettys , Olivier Dapremont , Aslam A. Malik
IPC分类号： C07D401/02
CPC分类号： C07D213/53 , C07D213/81
摘要： A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl) -2-oxapropanein high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di (1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3 -(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.
摘要翻译：通过向双卤代甲醚中加入吡啶醛肟制备1-（羟基亚氨基甲基-1-吡啶基）-3-（卤代甲基）-2-氧杂丙烷的卤化物盐，使双 - 卤代甲醚在整个过程中保持过量加成。该方法产生1-（羟基亚氨基甲基-1-吡啶基）-3-（卤代甲基）-2-氧杂丙烷的卤化物盐，其产率和纯度高，这有助于其用作制备不对称取代的1,3- 二（1-吡啶基）-2-氧杂丙烷，一类通常用于各种毒性剂的解毒剂的化合物。该类的突出成员是1-（2-羟基亚氨基甲基-1-吡啶基）-3-（4-氨基甲酰基-1-吡啶基）-2-氧杂丙烷的二甲基磺酸盐。公开了使用巯基烷基官能化聚合物作为优选的金属离子清除剂，用于制造这些化合物的最终纯化步骤。

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